The Cdk inhibitors p25rum1 and p40SIC1 are functional homologues that play similar roles in the regulation of the cell cycle in fission and budding yeast.
p25rum1 and p40SIC1 are specific inhibitors of p34(cdc2/CDC28) kinase complexes with B-type cyclins that play a central role in the regulation of the G1 phase of the cell cycle. We show here that low levels of expression of SIC1 in Schizosaccharomyces pombe rescues all the phenotypes of cells lacking the rum1+ gene. In addition, high level expression of SIC1 in S. pombe induces extra rounds of DNA replication without mitosis, a phenotype very similar to the overexpression of rum1+. Transient expression of rum1+ in S. cerevisiae restores the G1 arrest phenotype of cdc4 sic1Delta double mutants. Overproduction of rum1+ in Saccharomyces cerevisiae causes a cell cycle block in G1 with a phenotype similar to inactivation of all the Clb cyclins. Finally, we have mapped the cyclin interacting domain and Cdk inhibitory domain to a region of about 80 amino acids in p25rum1 that has significant homology to the C-terminal domain of p40SIC1. All these observations suggest that fission yeast p25rum1 and budding yeast p40SIC1 define a family of Cdk inhibitors that specifically down regulate cyclin B/Cdk1 during the G1 phase of the cell cycle.
Sánchez-Díaz
A
A
Instituto de Microbiología Bioquímica, CSIC/Universidad de Salamanca, Edificio Departamental, Campus Miguel de Unamuno, Salamanca, Spain.
González
I
I
Arellano
M
M
Moreno
S
S
D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D017124:Conserved Sequence; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D016213:Cyclins / Q000037:antagonists & inhibitors; D005656:Fungal Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D017353:Gene Deletion; D010641:Phenotype; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins; D012568:Schizosaccharomyces / Q000166:cytology / Q000502:physiology*; D029702:Schizosaccharomyces pombe Proteins; D017386:Sequence Homology, Amino Acid
D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D016213:Cyclins; D005656:Fungal Proteins; C086077:Rum1 protein, S pombe; C086926:SIC1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D018844:Cyclin-Dependent Kinases